Unique risk factors for insertional mutagenesis in a mouse model of XSCID gene therapy.

ABSTRACT: Although gene therapy can cure patients with severe combined immunodeficiency (SCID) syndromes, the clinical occurrence of T cell malignancies due to insertional mutagenesis has raised concerns about the safety of gene therapy. Several key questions have remained unanswered: (i) are there unique risk factors for X-linked SCID (XSCID) gene therapy that increase the risk of insertional mutagenesis; (ii) what other genetic lesions may contribute to transformation; and (iii) what systems can be used to test different vectors for their relative safety? To address these questions, we have developed an XSCID mouse model in which both the Arf tumor-suppressor gene and the gammac gene were ablated. Gene therapy in this animal model recapitulates the high incidence of integration-dependent, T cell t

SUBMITTER: Shou Y 

PROVIDER: S-EPMC1518804 | biostudies-literature | 2006 Aug

REPOSITORIES: biostudies-literature